Development

The set of standard terms below can be applied to each developing structure in each species covered in the ontology. However it is generally not practical to implement every term for every structure, since this would lead to a massive proliferation of terms. Where one term e.g. x development, is present, the rest of the terms for the development of x are considered to be implied, without having actually been implemented. Further terms are generally only implemented when they are required for annotation. To see an example of a more full implementation please see the children of mesoderm development, which cover the development of the mesoderm, and the axial, paraxial, and intermediate mesoderm.

This development node structure was agreed upon in 2003 and is gradually being retrofitted. Where terms appear not to conform to it, this may be because they have not yet been retrofitted, or because their development includes an exception to the normal model. Any questions about the development terms should be posted on the GO curator requests tracker.

Terms and Structure

This is the structure for development terms involving tissues, organs and organisms (based on this SourceForge discussion and this SourceForge discussion ).

  • x development
    • [p]z cell differentiation (where z is a cell that is part_of x)
    • [p] x morphogenesis
      • [p] x formation
        • [p] y cell differentiation (where y is a cell of the primordial structure)
      • [p] x structural organization
    • [p] x maturation

This is the structure for development terms involving cells (agreed at the St. Croix consortium meeting).

  • cellular process
    • [i] cell differentiation
      • [p] cell fate commitment
        • [p] cell fate specification
        • [p] cell fate determination
      • [p] cell development
        • [p] cellular morphogenesis during differentiation
        • [p] cell maturation

Standard Definitions

On implementation, each of the standard definitions below should be followed by a brief summary of the purpose of the structure, and also, where relevant, the characteristics marking its initial formation and its arrival at the mature state. If the common usage does not conform to GO term name syntax, then it is helpful to add an exact synonym with GO syntax.

x development
The process whose specific outcome is the progression of the x over time, from its formation to the mature structure.
x morphogenesis
The process in which the anatomical structures of x are generated and organized.
x formation
The process that gives rise to x. This process pertains to the initial formation of a structure from unspecified parts.
x structural organization
The process that contributes to creating the structural organization of x. This process pertains to the physical shaping of a rudimentary structure.
x maturation
A developmental process, independent of morphogenetic (shape) change, that is required for x to attain its fully functional state. [description of x]
[cell type] cell differentiation
The process whereby a relatively unspecialized cell acquires specialized features of a [cell type] cell. (N.B. This may be development of [cell type] cell type or a set of cells of [cell type] cell type. This will involve the change of a cell or set of cells from one cell identity to another.)
[cell type] cell fate commitment
The process whereby the developmental fate of a cell becomes restricted such that it will develop into a [cell type] cell.
[cell type] cell fate specification
The process whereby a cell becomes capable of differentiating autonomously into a [cell type] cell in an environment that is neutral with respect to the developmental pathway. Upon specification, the cell fate can be reversed.
[cell type] cell fate determination
The process whereby a cell becomes capable of differentiating autonomously into a [cell type] cell regardless of its environment; upon determination, the cell fate cannot be reversed.
[cell type] cell development
The process aimed at the progression of a [cell type] cell over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell.
[cell type] cell morphogenesis during differentiation
The process in which the structures of a [cell type] cell are generated and organized. This process occurs while the initially relatively unspecialized cell is acquiring the specialized features of a [cell type] cell.
[cell type] cell maturation
A developmental process, independent of morphogenetic (shape) change, that is required for a [cell type] cell to attain its fully functional state. [description of [cell type]]
Note:
See Other Miscellaneous Standard Defs below for x biogenesis.

Qualifiers

The following qualifiers can be used with morphogenesis.

embryonic x morphogenesis
The process, occurring in the embryo, by which the anatomical structures of x are generated and organized.
larval x morphogenesis
The process, occurring in the larva, by which the anatomical structures of x are generated and organized.
post-embryonic x morphogenesis
The process, occurring after embryonic development [and prior to (e.g. larval) development], by which the anatomical structures of x are generated and organized.

Development vs Morphogenesis

The concepts of development and morphogenesis may at first seem synonymous. On further thought however, it becomes apparent that at the level of tissues, organs and organisms, development encompasses much more than just the generation and organization of anatomical structures. In some instances it includes steps called maturation which may include a wide range of processes, one of which is described below.

Seed development

Seeds are complex structures whose development includes both a morphogenesis and maturation step (this SourceForge discussion ).

A. Seed Morphogenesis

The morphogenesis phase includes generation and organization steps, as described in Developmental Biology, 6th Edition (Scott F. Gilbert):

  • To establish the basic body plan. Radial patterning produces three tissue systems, and axial patterning establishes the apical-basal (shoot-root) axis.
  • To set aside meristematic tissue for postembryonic elaboration of the body structure (leaves, roots, flowers, etc.).
  • To establish an accessible food reserve for the germinating embryo until it becomes autotrophic.

B. Seed Maturation

In many species the fully formed seed enters a physiological state of dormancy, and this is an example of a maturation process. At this point morphogenesis is over, but development continues with onset of dormancy phase.

diag-seed-dormancy.gif

Formation vs Development

Confusion often arises about the role of formation in the development process. Formation would have to do with the processes that establish a tissue. A couple of examples of these would be primary embryonic induction and epithelial to mesenchymal transition. As in other parts of the development graph, the development of a tissue would include much more than this, including morphogenic shaping of cell layers, patterning, selective apoptosis etc, depending on the tissue. Therefore formation terms are made as parts of the morphogenesis terms, and the full morphogenetic process also requires structural organization step to fully generate and organize the structure.

Structural Organization vs Morphogenesis

These are not synonymous because the structure has to be initially formed before it can increase in size and be organized. Morphogenesis covers both formation and structural development.

What is maturation?

The maturation term was instantiated for cases in which a cell is not changing morphologically (changing shape), but is still developing. The remaining development steps involve synthesis of gene products that will enable the cell or structure to become fully functional.

One example of this is the maturation of the epithelial cells of the intestinal crypts. These are born at the bottom of the crypts as columnar epithelial cells. The process making them conform to this shape is be their morphogenesis. As they mature, they don't change shape, but they move up along the villus due to the death of the cells at the tip and the birth of new cells at the bottom.

While they are moving up, they are synthesizing the gene products that make them functional absorptive cells. This is part of their maturation. Eventually they apoptose. This is also part of their maturation.

Another example would be a neuron that has already fully extended its axons and dendrites (neuron morphogenesis) and is receiving signals about what kind of receptors and neurotransmitters it is going to make. This is maturation because the process doesn't have anything to do with creating the shape of the cell but is required for attainment of full function.

To summarize, the maturation terms capture the processes that are involved in a cell becoming fully functional but that aren't directly related to the changes in shape of the cell.

Metamorphosis vs Morphogenesis

The concepts of metamorphosis and morphogenesis are closely related but have some key differences.

  • [i] x development
    • [p] x morphogenesis
      • [i] x metamorphosis

Metamorphosis terms refer to the radical change in shape of a whole organism, for example metamorphosis of the whole tadpole to the whole frog. Morphogenesis terms capture the processes in which the shape or form of a whole organism or part of an organism is gradually formed, for example morphogenesis of a worm, a leaf, or a limb.

x metamorphosis
A change of shape or structure of the whole organism from one developmental stage to another, particularly the rapid post embryonic structural transformation from larval to adult form.
x morphogenesis
The process in which the anatomical structures of x are generated and organized.

Note that morphogenesis terms always include the name of the mature anatomical part in the term name.

Imaginal Discs

The fly imaginal disc terms are a fusion of these two concepts as the process of fly imaginal disc morphogenesis changes the shape of a part of an organism (imaginal disc) very radically. In addition to this, the standard morphogenesis definitions will not work for imaginal disc morphogenesis as the relationship of the initial structures to the mature structures is not one-to-one. One disc can contribute to more than one mature structure, and one structure can be formed from more than one disc. For example, the Drosophila eye-antennal disc gives rise to the eye, antenna, head capsule and maxillary palps. In higher Diptera, primordia contained in different imaginal discs (labial disc, clypeolabral bud) participate in the formation of the proboscis.

Because of this, the research community investigates these processes by looking at the morphogenesis of each disc as a whole, through time, rather than looking at the formation of each individual mature structure. This means that the research results available to be annotated to the GO tend to be couched in terms of disc morphogenesis rather than in terms of morphogenesis of a single anatomical part that happens to be derived from a disc.

The standard morphogenesis terms in GO have the mature anatomical part in the term name and define the process as the steps leading to the final form of that structure. This is not possible in the case of fly imaginal discs and so a slight modification had been made to accommodate the difference in research method, but preserve the standard temporal factors in the description of the process.

Imaginal disc terms receive the name x imaginal disc morphogenesis and the exact synonym x imaginal disc metamorphosis, in which the x refers to the initial anatomical structure. Their definition is very similar to the morphogenesis standard definition but with a key difference:

x morphogenesis
The process in which the anatomical structures of x are generated and organized.
x metamorphosis
A change of shape or structure of the whole organism from one developmental stage to another, particularly the rapid post embryonic structural transformation from larval to adult form.
x imaginal disc morphogenesis
The process in which the anatomical structures derived from the x disc are generated and organized. This includes the transformation of a x imaginal disc from a monolayered epithelium in the larvae of holometabolous insects into the recognizable adult structures a, b, c, d and e. exact synonym: x imaginal disc metamorphosis

The definition still captures the morphogenesis of the mature structure but the immature structure is the one explicitly named in the term name and definition, as in the biological literature. Anyone annotating to these terms should bear in mind that the imaginal disc terms are to be used for annotation of gene products involved in the processes that enable the morphogenesis of the disc (mentioned in the term name) to another anatomical part. This is different from the standard morphogenesis terms in which the term is intended to be used for annotation of gene products involved in morphogenesis bringing about the shape of the part mentioned in the term name. It is important that these differences should be borne in mind while annotating.

In summary, when using these terms, as with all GO terms, please read the definition carefully.

Differentiation vs Cell development

Q: What is the difference between 'cell differentiation' and 'cell development'?
A: Cell development should NOT include the steps involved in committing a cell to a specific fate. Differentiation includes the processes involved in commitment. Development is what the cell does once it is committed to a given fate.

To express this our standard structure is like this:

  • [i] cell differentiation
    • [p] cell fate commitment
      • [p] cell development

When does development start?

The situation above illustrates a central point in capturing developmental processes in an ontology. The conceptual difficulty here is deciding when the development of x begins and when it ends. For example, the embryogenesis of my mother could be considered to be part of my development, or gastrulation could be considered to be part of kidney development. Although my mother's embryogenesis led to the final state that was me, and gastrulation leads to the final state of a kidney, clearly there has to be a cut-off somewhere.

That cut off is determined by how the class development differs from the class X development. Clearly for the case of me from a biological perspective, the start can be set at the fertilised egg (although that is still argued in legal circles, and ontologists might argue that the individual is not established until the point when it is too late for the egg to divide to produce two individuals). But what about the development of a specific type of cell? It makes sense to set the start of development of a specific type of cell as occurring once the cell has been committed to its fate. Otherwise we may be considering processes that might not necessarily end in the maturation of that cell type. This is how we have expressed the situation in the process ontology.

Should we represent cell lineage in the process ontology?

One further related question that we often come up against is whether to try to represent cell lineage in the development node of the process ontology. Lineage relationships are better represented in other ontologies such as in the cell ontology or in an anatomical ontology. The sum of all processes that lead up to something can then be computed based on those relationships. For example, you may want to know about gene products involved in neuron development and you may want to include the development of all the precursors of the neuron. To do this you can use a combination of the cell type ontology (which encodes lineage information) and the development node of the process ontology (which captures information on development). Source: SourceForge discussion

What is the difference between 'cell differentiation' and 'cell development'?
Cell development should NOT include the steps involved in committing a cell to a specific fate. Differentiation includes the processes involved in commitment. Development is what the cell does once it is committed to a given fate.

Cell fate specification, determination and commitment

The differences between cell fate commitment, cell fate specification and cell fate determination are fairly subtle and so they are explained below.

  • [i] cell differentiation
    • [p] cell fate commitment
      • [p] cell fate specification
      • [p] cell fate determination

Source: St. Croix consortium meeting minutes + subsequent changes.

cell differentiation
The process whereby relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organisms life history.
cell fate commitment
The commitment of cells to specific cell fates and their capacity to differentiate into particular kinds of cells. Positional information is established through protein signals that emanate from a localized source within a cell (the initial one-cell zygote) or within a developmental field.
cell fate specification
The process involved in the specification of cell identity. Once specification has taken place, a cell will be committed to differentiate down a specific pathway if left in its normal environment.
cell fate determination
The process involved in cell fate commitment. Once determination has taken place, a cell becomes committed to differentiate down a particular pathway regardless of its environment.

Cell maturation and differentiation of derivative cell types

What is the relationship between maturation of a cell type and differentiation of the derivative cell type in the GO process ontology?

To figure this out we have to think about how one cell type arises from another, and then consider how this information is represented in the GO process ontology and in the cell type ontology.

If we consider a cell type A, the differentiation of this cell will include all the steps common to cell differentiation (standard structure and Figure 1). During the differentiation of a cell type A it is possible that some individual cells of the population of A cells will undergo a change of identity to become committed to other cell fates, B and C (Figure 1). This change in identity can occur at any time during the differentiation of a cell of type A. For example in Figure 1 the change of identity is shown as occurring at the end of an instance of cell type A's fate determination step (one A cell giving rise to an one B cell that will then develop). This change in identity is the cell fate commitment of cell type B.

Another instance of cell type A may further mature and be recommitted at another time to give rise to an instance of a cell type C. So, in this case, a cell type A can give rise to both cell type B and cell type C. The lineage information is not reflected in the biological process ontology, but is rather reflected in the cell ontology.

diag-cell-dev.png

Figure 1: the steps in the differentiation of the three cell types A, B and C. Cell types B and C are derived from A.

The figure shows that the differentiation of a cell type begins as soon as the process of cell fate specification occurs. In the GO process ontology this would be represented as three separate cell differentiation terms (with appropriate child terms) without any lineage information as follows:

diag-differentiation.png

Figure 2: cell differentiation terms and child terms for cell types A, B and C. The background is highlighted in three colours to make it easier to see where the terms for the three different cell types are.

The lineage information would be captured in the cell type ontology as follows ([d]represents the relationship develops_from):

  • [i] cell by lineage
    • [i] A cell
      • [d] B cell
      • [d] C cell

A part_of problem for cell differentiation

There is a potential problem with the use of necessarily is_part in the relationship between the differentiation terms and their parent development terms. If cell type X cell differentiation occurs as part of the development of two different types of tissue (e.g. anatomical structure A development and anatomical structure B development) then that would not work with the necessarily is_part kind of part_of relationship that is used in GO. With necessarily is_part, X cell differentiation doesn't always have to occur during B development, but X cell differentiation must only occur as part of B development.

  • [i] anatomical structure A development
    • [p] cell type X cell differentiation
  • [i] anatomical structure B development
    • [p] cell type X cell differentiation

This structure is incorrect.

The solution: A separate term must be made for the differentiation of the cell type in every different organ in which it is found. The standard composition of these terms can be summarized as:

[anatomical structure] + [cell type] + cell differentiation

  • [i] anatomical structure A development
    • [p] anatomical structure A cell type X cell differentiation
...
  • [i] anatomical structure B development
    • [p] anatomical structure B cell type X cell differentiation
...
  • [i] cell type X cell differentiation
    • [i] anatomical structure A cell type X cell differentiation
    • [i] anatomical structure B cell type X cell differentiation

A practical example:

  • [i] lung epithelium development
    • [p] lung epithelial cell differentiation
...
  • [i] glomerular epithelium development
    • [p] glomerular epithelial cell differentiation
...
  • [i] epithelial cell differentiation
    • [i] heart epithelial cell differentiation
    • [i] glomerular epithelial cell differentiation

History of the Development node

  • 2002: Many of the 'development' and 'morphogenesis' terms were written before we had clearly defined the difference between these two concepts and as a consequence both their positions in the ontology and their definions were basically interchangeable. Many of the other standard terms under the development node were also defined using the names of different terms rather than a clear and correct definition.
  • 2003: The development interest group developed standard definitions and a standard ontology structure for the terms under the development node.
  • 2004: Implementation of the structure began as follows:
    • The terms x cell fate commitment, x cell fate specification and x cell fate determination were given their standard definitions.
    • x development terms were given their standard definition.
    • x morphogenesis terms with definitions that did not include the word 'development' were given their standard definition.
    • x cell differentiation terms were given their standard definitions.
    • x structural organization generic parent was added for child terms already present.
  • 2005: Terms covering the metamorphosis of fly imaginal discs were all converted to morphogenesis terms, with metamorphosis as synonyms. The top metamorphosis terms were retained for use in describing whole body metamorphosis.
  • 2005-2006: Morphogenesis standard graph and definitions retrofitted.
  • < 2006: Maturation standard graph and definitions retrofitted.